Cleavable Hydrophobic Anchors Optimize Immunomodulatory Effects of Oligonucleotides.

ABSTRACT: Oligonucleotides (ODNs) are useful in a wide variety of biomedical applications, spanning diagnostics, and therapeutics but are susceptible to nuclease degradation and exhibit poor cellular uptake. Strategies that involve phosphorothioate (PS) backbone modifications and hydrophobic group conjugations have been used to enhance the stability and bioavailability of ODNs. However, improved ODN cellular delivery has not always correlated well with enhancing therapeutic efficacy, particularly in the context of immune modulation. Herein, we propose a theory to explain why this is the case and subsequently present a strategy based upon it to incorporate cleavable linkages between functional ODNs and hydrophobic moieties to simultaneously enhance cellular uptake and improve ODN functionality. Speci

SUBMITTER: Luo T 

PROVIDER: S-EPMC12720423 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature